A simplified MyProstateScore2.0 for high-grade prostate cancer
<b>Background:</b> The limited diagnostic accuracy of prostate-specific antigen screening for prostate cancer (PCa) has prompted innovative solutions, such as the state-of-the-art 18-gene urine test for clinically-significant PCa (MyProstateScore2.0 (MPS2)). <b>Objective:</b> We aim to develop a non-invasive biomarker test, the simplified MPS2 (sMPS2), which achieves similar state-of-the-art accuracy as MPS2 for predicting high-grade PCa but requires substantially fewer genes than the 18-gene MPS2 to improve its accessibility for routine clinical care. <b>Methods:</b> We grounded the development of sMPS2 in the Predictability, Computability, and Stability (PCS) framework for veridical data science. Under this framework, we stress-tested the development of sMPS2 across various data preprocessing and modeling choices and developed a stability-driven PCS ranking procedure for selecting the most predictive and robust genes for use in sMPS2. <b>Results:</b> The final sMPS2 model consisted of 7 genes and achieved a 0.784 AUROC (95% confidence interval, 0.742-0.825) for predicting high-grade PCa on a blinded external validation cohort. This is only 2.3% lower than the 18-gene MPS2, which is similar in magnitude to the 1-2% in uncertainty induced by different data preprocessing choices. <b>Conclusions:</b> The 7-gene sMPS2 provides a unique opportunity to expand the reach and adoption of non-invasive PCa screening.
Authors
- Cassie Xie (ORCID: https://orcid.org/0000-0002-5921-6266)
- Arul M. Chinnaiyan (ORCID: https://orcid.org/0000-0001-9282-3415)
- Jeffrey J. Tosoian (ORCID: https://orcid.org/0000-0002-7614-9931)
- Tiffany M. Tang (ORCID: https://orcid.org/0000-0002-8079-6867)
- Lanbo Xiao
- Ziding Feng (ORCID: https://orcid.org/0000-0003-3051-8882)
- Yuping Zhang (ORCID: https://orcid.org/0009-0004-3833-7474)
- Bin Yu (ORCID: https://orcid.org/0000-0002-8888-4060)
- Sudhir Srivastava (ORCID: https://orcid.org/0000-0002-7798-9772)
- Yingye Zheng
- Martin G. Sanda (ORCID: https://orcid.org/0000-0003-4288-5786)
- John T Wei
- Ana Kenney
- Javed Siddiqui (ORCID: https://orcid.org/0009-0004-8251-4829)
Institutions
- National Institutes of Health (US)
- Howard Hughes Medical Institute (US)
- Emory University (US)
- Vanderbilt University (US)
- University of California, Irvine (US)
- University of Michigan (US)
- Fred Hutch Cancer Center (US)
- Michigan Center for Translational Pathology (US)
- Vanderbilt-Ingram Cancer Center
- Vanderbilt University Medical Center (US)
- University of California, Berkeley (US)
Publication Details
- Journal
- Cancer Biomarkers
- Published
- 2025-01-01
- DOI
- https://doi.org/10.1177/18758592241308755
- Citations
- 1
- Primary Topic
- Prostate Cancer Treatment and Research
- Type
- article
- Field-Weighted Citation Impact
- 1.52
Funders
- National Science Foundation
- Howard Hughes Medical Institute
- American Cancer Society
- Prostate Cancer Foundation
- Vanderbilt University
- Johns Hopkins University
- Peking University
- National Institutes of Health
- Peking University Health Science Center
- National Cancer Institute
- Division of Mathematical Sciences